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Single-cell RNA sequencing of antigen specific CD4+ T cells induced by high vs low doses of MHC-II restricted neoantigens

ABSTRACT: Single-cell RNA sequencing of antigen specific CD4+ T cells induced by high vs low doses of MHC-II restricted neoantigens

PROVIDER: PRJNA1116136 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR29163060_1.fastq.gz	Fastqsanger.gz
	SRR29163060_2.fastq.gz	Fastqsanger.gz
	SRR29163061_1.fastq.gz	Fastqsanger.gz
	SRR29163061_2.fastq.gz	Fastqsanger.gz
	SRR29163062_1.fastq.gz	Fastqsanger.gz

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Single-cell RNA sequencing of antigen specific CD4+ T cells induced by high vs low doses of MHC-II restricted neoantigens

Project description:Here, we report the impact of the dose of the MHC-II restricted neoantigens on the phenotypic and the effector function of tumor-specific CD4 T cells. Whereas vaccines containing low doses of MHC-II-restricted neoantigen (LDVax) generated helper CD4 T cells that promote the proliferation and the cytotoxic functions of CD8 T cells, vaccines containing high doses of MHC-II restricted neoantigen (HDVax) elicited type 1 regulatory T cells that suppress the antitumor immunity.

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RNA sequencing of antigen specific CD4+ T cells induced by high vs low doses of MHC-II restricted neoantigens

Project description:RNA sequencing of antigen specific CD4+ T cells induced by high vs low doses of MHC-II restricted neoantigens

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Gene expresion profile of different clusters of antigen specific CD4+ T cells induced by vaccines containing high doses of MHC-II restricted neoantigens

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Antigen Presentation Profiling Reveals T-cell Recognition of Lymphoma Immunoglobulin Neoantigens

Project description:Cancer somatic mutations can generate neoantigens that distinguish malignant from normal cells. Such neoantigens have been implicated in response to immunotherapies including immune checkpoint blockade, yet their identification and validation remains challenging. Here we discover neoantigens in human mantle cell lymphomas using an integrated strategy for genomic and proteomic tumor antigen discovery that interrogates peptides presented within the tumor major histocompatibility complex (MHC) class I and class II molecules. We applied this approach to systematically identify neoantigen peptides in diagnostic tumor specimens from 17 patients and several cell lines. Remarkably, the discovered neoantigenic peptides were invariably derived from the lymphoma immunoglobulin (Ig) heavy or light chain variable regions. Although we could identify MHC presentation of private germline polymorphic alleles, no mutated peptides were recovered from non-Ig somatically mutated genes. The immunoglobulin variable region somatic mutations were almost exclusively presented by MHC-II. We found T-cells specific for an immunoglobulin-derived neoantigen in the blood of a patient using MHC-II tetramers, and these T-cell clones expanded in frequency following tumor vaccination. These results demonstrate that an integrative approach combining MHC isolation, peptide identification and exome sequencing is an effective platform to uncover tumor neoantigens. Application of this strategy to human lymphoma implicates immunoglobulin neoantigens as targets for lymphoma immunotherapy.

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Antigen Presentation Profiling Reveals T-cell Recognition of Lymphoma Immunoglobulin Neoantigens

Project description:Cancer somatic mutations can generate neoantigens that distinguish malignant from normal cells. Such neoantigens have been implicated in response to immunotherapies including immune checkpoint blockade, yet their identification and validation remains challenging. Here we discover neoantigens in human mantle cell lymphomas using an integrated strategy for genomic and proteomic tumor antigen discovery that interrogates peptides presented within the tumor major histocompatibility complex (MHC) class I and class II molecules. We applied this approach to systematically identify neoantigen peptides in diagnostic tumor specimens from 17 patients. Remarkably, the 52 discovered neoantigenic peptides were invariably derived from the lymphoma immunoglobulin (Ig) heavy or light chain variable regions. Although we could identify MHC presentation of private germline polymorphic alleles, no mutated peptides were recovered from non-Ig somatically mutated genes. The immunoglobulin variable region somatic mutations were almost exclusively presented by MHC-II. We found T-cells specific for an immunoglobulin-derived neoantigen in the blood of a patient using MHC-II tetramers, and these T-cell clones expanded in frequency following tumor vaccination. These results demonstrate that an integrative approach combining MHC isolation, peptide identification and exome sequencing is an effective platform to uncover tumor neoantigens. Application of this strategy to human lymphoma implicates immunoglobulin neoantigens as targets for lymphoma immunotherapy.

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RNA sequencing of antigen specific CD4+ T cells induced by high vs low doses of MHC-II restricted neoantigens

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